Embryology of the Urogenital Systems Flashcards
What type of embryonic tissue does the urinary (and genital) system develop from?
Intermediate mesoderm of trilaminar disc.
What does intermediate mesoderm separate from?
From lateral and paraxial mesoderm during folding and forms urogenital ridge.
What forms the urogenital ridge?
Intermediate mesoderm separates from lateral and paraxial mesoderm during folding and forms urogenital ridge.
At what week of development is the mesonephros present and functional?
weeks 6 -10
After week 10 of development, the mesonephros degenerates except for?
> the duct system will contribute to part of the male genital system (ductus deferens).
> some vestigial structures in the female.
Even though the metanephros is not functional in women, what is it still important?
Because it contributes to the development of the ureter.
True or False:
Renogenesis involves a process of reciprocal induction, which is not retinoic acid dependent.
False - renogenesis involves a process of reciprocal induction, which IS retinoic acid dependent.
What establishes a renogenic region within the intermediate mesoderm in the tail of the embryo?
Cranial-caudal patterning
What is the metanephric blastema?
renogenic mesoderm is the METANEPHRIC BLASTEMA
What does the metanephric blastema secrete?
Secretes growth factors that induce growth of the URETERIC BUD from the caudal portion of the mesonephric duct.
What induces growth of the ureteric bud from the caudal portion of the mesonephric duct?
the metanephric blastema secretes growth factors that induce growth
True or False:
The ureteric bud proliferates and responds by secreting growth factors that stimulates proliferation and then differentiation of the metanephric blastema into glomeruli and kidney tubules.
True
What differentiates into glomeruli and kidney tubules?
metanephric blastema
What can cause inhibition of ureteric bud growth and renal hypoplasia or agenesis?
perturbations in any aspect of these inductive events (e.g., mutations of either metanephric or ureteric factors or disruption of retinoic acid signaling
At which week of development does blood plasma from glomerular capillaries begins to be filtered?
10th week
Urine is produced by the 10th week of development, but what is the primary function of the urine?
Primary function is not to clear waste (placenta) but to supplement production of amniotic fluid.
What may oligohydramnios (insufficient amount of amniotic fluid indicate?
May indicate bilateral renal agenesis or urethral obstruction.
What is oligohydramnios?
insufficient amount of amniotic fluid
What is the in utero function of the metanephros?
To filter blood plasma from glomerular capillaries at the 10th week of development, which produces urine. This urine is supplemental production of amniotic fluid.
List the clinical considerations that we are responsible for in this lecture.
- accessory renal vessels
- renal agenesis
- renal ectopia
- renal fusion
- urachal fistula or cyst
- Wilms tumor
In what percentage of individuals do accessory renal vessels occur and from where do they arise?
10% of individuals and 98% arise from the abdominal aorta.
Most enter the renal pelvis and pose little problem
Where can aberrant renal arteries enter the kidney that pose problems?
Upper or lower poles of the kidney.
Aberrant arteries to the inferior pole of the kidney (4-6%) may be caused by what?
Obstruction of the ureter and may cause an intermittent or continuous obstruction to urinary drainage from the renal pelvis.
True or False:
Aberrant renal vessels enter the kidney independently from the primary renal vessels.
True
You know that kidneys are formed in the pelvis and ascend to the lumbar region, but with progressive revascularization from what?
Common iliac and aorta.
Where are kidneys formed and where do they ascend to?
Kidneys are formed in the pelvis but ascend to lumbar region with progressive revascularization from common iliac and aorta.
What two things cause Potter’s syndrome (pulmonary hypoplasia)?
- Oligohydramnios
- Fetal compression
What causes amnion nodosum?
Oligohydramnios
Is Potter’s syndrome diagnosed in utero?
Yes
What does renal fusion prevent in normal kidney development?
Normal rotation of kidney.
In patients with renal fusion, from what arteries is typical abnormal blood supply coming from?
Usually from middle sacral or common iliac arteries.
What is the typical shape (defining structure) of a kidney in a patient with renal fusion?
Horseshoe kidney
What percentage of horseshoe kidneys are fused at the lower pole?
90%
What landmark is horseshoe kidneys typically found inferior to?
Inferior mesenteric artery.
because the horseshoe kidney gets stuck under the inferior mesenteric artery when the kidney is ascending during development
What is Wilms’ tumor and who is usually affected?
Cancer of the kidney and usually affects children under the age of 5.
A mutation in what gene causes a Wilms’ tumor?
Mutations in the WT1 gene.
Give the diagnosis:
A 3 month-old previously healthy boy presented with hematuria. A renal ultrasound, and subsequent chest, abdomen, and pelvis CT exam demonstrated a large heterogeneous right renal mass.
Wilms’ Tumor
Once the cloaca is divided by the urorectal septum, what does the dorsal (inferior) portion develop into?
Rectum and Anal Canal
Once the cloaca is divided by the urorectal septum, what does the ventral (superior) portion develop into?
Bladder and Urogenital Sinus
which will give rise to the bladder and lower urogenital tracts (prostatic and penile urethrae in males; urethra and lower vagina in females)
What does the bladder and urogenital sinus give rise to?
Bladder and lower urogenital tracts (prostatic and penile urethrae in males; urethra and lower vagina in females).
What develops into the bladder and urogenital sinus?
The ventral (superior) portion of the cloaca once it has been divided by the urorectal septum.
What develops into the rectum and anal canal?
The dorsal (inferior) portion of the cloaca once it has been divided by the urorectal septum.
What gives rise to the bladder and lower urogenital tracts (prostatic and penile urethrae in males; urethra and lower vagina in females)?
Bladder and Urogenital Sinus.
Before the cloaca is divided, what is it?
A common outflow tract for GI and bladder.
Between what weeks in development does the mesonephric duct and ureteric bud incorporate into the posterior wall of the urinary bladder?
4-6 weeks
What are the difference between the openings of the ureteric buds and mesonephric ducts?
> Ureteric buds - open into bladder wall
Mesonephric ducts - open more inferiorly into the pelvic urethra
ductus deferens doesn’t open into the bladder
What forms the trigone of the urinary bladder?
The triangular region of the incorporated mesonephric duct incorporated in the bladder wall forms the trigone.
Why do you want the ductus deferens inferior to the bladder?
So the bladder can get larger and to make sure that semen and urine are not mixing.
What is a urachal fistula or cyst?
> Bladder is continuous superiorly with allantois (which should collapse and become the urachus).
> The urachus may remain patent throughout its length (urachal fistula) or only at an end (urachal sinus).
> Remnants of the urachal lumen may also give rise to urachal cysts. These usually present as an abdominal mass.
What is a way to diagnose a urachal fistula or cyst?
If urine is coming out of the umbilical cord.
True of False:
The genotype of the embryo is established at fertilization.
True
What state does the embryo remain in during weeks 1-6?
Remains in a undifferentiated state.
At what week of gestation does phenotypic sexual differentiation begin?
Week 7
At what week of gestation can the male and female external genitalia be recognized?
Week 12
At what week of gestation is phenotypic differentiation complete?
Week 20
What does the Wolffian (mesonephric) duct develop into?
- epididymis
- vas deferens
- seminal vesicle
- ejaculatory duct
What does the Mullerian (paramesonephric) duct develop into?
- fallopian tubes
- uterus
- upper part of vagina
Where is the SRY encoded on the Y-chromosome?
On the sex-determining region.
What does the synthesis of SRY protein (testis-determining factor, TDF) trigger?
Male Development
What happens if SRY protein is not synthesized?
Female path is followed.
Which sex is the basic (default) developmental pathway?
Female
True of False:
In the development of genital ducts, two pairs of ducts are present in both sexes.
True
True of False:
Both pairs of ducts are present during the indifferent stage (weeks 1-6).
True
Which ducts play the most important role in the male?
mesonephric ducts
Which ducts play the most important role in the female?
paramesonephric ducts
What are the 4 stages of sex determination in mammals?
1) genetic sex
2) gonadal sex
3) phenotypic sex (internal and external)
4) behavioral and metabolic sex
Which 3 tissues do gonads develop from?
- epithelium of intraembryonic coelom
- intermediate mesoderm
- primordial germ cells
During the development of gonads, what does the primordial germ cells from the mesoderm of the yolk sac invade?
The dorsal mesentery and migrate to urogenital ridges.
Primary sex cords are aggregates of what?
Supporting cells (hormone secreting cells).
What is a phallus?
clitoris or penis
What are (uro)genital folds?
labis minora or shaft of the penis
What are labioscrotal (genital) swellings?
labis majora or scrotum
List 6 paramesonephric duct anomalies.
> uterus didelphys with double vagina > uterus arcuatus > uterus bicornis > uterus bicornis unicollis and 1 rudimentary horn > atresia of cervix > atresia of vagina
What can cause cervical or vaginal atresia?
Partial or total atresia of the distal portion of both ducts.
True of False:
46, XY can have persistence of paramesonephric ducts if the circulating levels of AMH are low or there is an abnormal response to normal AMH.
True
What is Mullerian agenesis caused by?
Failure of the paramesonephric ducts to develop.
What does Mullerian agenesis result in?
Missing uterine tubes, uterus, and variable malformations of the upper portion of the vagina.
What is Mullerian agenesis also known as?
MRKH or Mayer-Rokitansky-Kuster-Hauser Syndrome
What is hypospadias caused by?
Incomplete fusion of the urethral folds.
What does incomplete fusion of the urethral folds cause?
hypospadias
What does hypospadias do to external genitalia?
Causes urethra to open onto the ventral aspect of the penis.
What can hypospadias result from? Hint: what causes incomplete fusion of the urethral folds?
Can result from inadequate androgen production or inadequate receptor sites for DHT.
What are the 4 types of hypospadias?
- glandular
- penile
- penoscrotal
- perineal
What are the characteristics of classic virilizing adrenal hyperplasia?
> female intersex
females (46, XX) with severe forms of adrenal hyperplasia have ambiguous genitalia at birth due to excess adrenal androgen production in utero.
Ambiguous genitalia ranges from complete fusion of the labioscrotal folds and a phallic urethra to only clitoromegaly, partial fusion of the labioscrotal folds, or both.
NO abnormalities of ovaries.
What does increased exposure to androgens result in?
- clitoral hypertrophy
- labioscrotal fusion
What is androgen insensitivity syndrome (AIS) - complete?
> An X-linked disorder in which receptors remain unresponsive to androgens.
> Despite normal levels of testosterone, the male foetus fails to masculinise.
> The external genitalia are feminine. Internally they possess non-functioning undescended testes.
> At puberty, secondary female sexual characteristics may appear due to estradiol from testosterone aromatization.
> It is common to perform gonadectomies at puberty and for them to receive hormone therapy, to be reared as female.
What does the degree of feminization depend on in patients with male (46, XY) with testes and feminized genitals?
Affected androgens and the amount of residual receptor function.
What is 5-alpha reductase deficiency (5-ARD)?
Autosomal recessive condition resulting in the inability to convert testosterone to the more physiologically active dihydrotestosterone (DHT).
What is 5-ARD often misdiagnosed as?
AIS
True of False:
Because DHT is required for the normal masculinization of the external genitalia in utero, genetic males with 5-ARD are born with ambiguous genitalia (underdevelopment of penis and scrotum or pseudovaginal perineoscrotal hypospadias).
True
Look at the course of development if SRY is expressed or not expressed.
Either male or female.
